Water soluble nanoparticles of hydrophilic and hydrophobic active materials and an apparatus and method for their production

Abstract

This invention provides a soluble nano-sized particles formed of a core (water-insoluble lipophilic compound or hydrophilic compound) and an amphiphilic polymer and which demonstrated improved solubility and / or stability. The lipophilic compound within the soluble nano-sized soluble (“solu-nanoparticles”) may consist of pharmaceutical compounds, food additives, cosmetics, agricultural products and veterinary products. The invention also provides novel methods for preparing the nano-sized soluble particles, as well as a novel chemical reactor for manufacturing an inclusion complex comprising the nano-sized soluble particles.

Description

FIELD OF THE INVENTION[0001]The invention is in the field of nanoparticles. More particularly, the invention relates to soluble nano-sized particles (“solu-nanoparticles”) and methods of producing solu-nanoparticles that render insoluble compounds solubilized in a medium otherwise not soluble.BACKGROUND OF THE INVENTION[0002]Two formidable barriers to effective drug delivery and hence to disease treatment, are solubility and stability. To be absorbed in the human body, a compound has to be soluble in both water and fats (lipids). Solubility in water is, however, often associated with poor fat solubility and vice versa.[0003]Over one third of drugs listed in the U.S. Pharmacopoeia and about 50% of new chemical entities (NCEs) are insoluble or poorly insoluble in water. Over 40% of drug molecules and drug compounds are insoluble in the human body. In spite of this, lipophilic drug substances having low water solubility are a growing drug class having increasing applicability in a vari...

AI Technical Summary

Benefits of technology

"The present invention provides a method for producing soluble nanoparticles by using water-soluble amphiphilic polymers that can form molecular complexes with lipophilic and hydrophilic compounds. These nanoparticles can be used in various applications such as pharmacology, food additives, cosmetics, and agriculture. The method involves using a chemical reactor to continuously circulate a polymer solution and the active compound, resulting in a high uniformity of the emulsion or suspension formed during the process. The inclusion complex formed using this method has the advantage of no new bonds formed and no existing bonds destroyed during the process. The ingredients used in the preparation of the complex are inexpensive, abundant, non-toxic, and safe for use in the surrounding environment."

Problems solved by technology

Two formidable barriers to effective drug delivery and hence to disease treatment, are solubility and stability.

Solubility in water is, however, often associated with poor fat solubility and vice versa.

Each of the existing companies focusing on these large and small molecules has its own restriction and limitations with regard to both large and small molecules on which they focus.

Solubility and stability issues are major formulation obstacles hindering the development of therapeutic agents.

These formulations are often irritating to the patient and may cause adverse reactions.

At times, these methods are inadequate for solubilizing enough of a quantity of a drug for a parenteral formulation.

Overdosage does, however waste a large amount of the active compound.

Poor bioavailability is a significant problem encountered in the development of pharmaceutical compositions, particularly those containing an active ingredient that is poorly soluble in water.

Although a number of solubilization technologies do exist, such as liposomes, cylcodextrins, microencapuslation, and dendrimers, each of these technologies has a number of significant disadvantages.

However, common problems encountered with liposomes include: low stability, short shelf-life, poor tissue specificity, and toxicity with non-native lipids.

Additionally, the uptake by phagocytic cells reduces circulation times. Furthermore, preparing liposome formulations that exhibit narrow size distribution has been formidable challenge under demanding conditions, as well as a costly one.

Also, membrane clogging often results during the production of larger volumes required for pharmaceutical production of a particular drug.

For a long time most cyclodextrins had been no more than scientific curiosities due to their limited availability and high price.

The disadvantages of the cyclodextrins, however, include: limited space available for the active molecule to be entrapped inside the core, lack of pure stability of the complex, limited availability in the marketplace, and high price.

The relatively high production cost needed for many of the formulations is, however, a significant disadvantage.

Problems associated with the use of polymers in micro- and nanoencapsulation include: the use of toxic emulgators in emulsions or dispersions, polymerization or the application of high shear forces during emulsification process, insufficient biocompatibility and biodegrability, balance of hydrophilic and hydrophobic moieties, etc.

These characteristics lead to insufficient drug release.

However, dendrimer technology is still in the research stage, and it is speculated that it will take years before the industry will apply this technology as a safe and efficient drug delivery system.

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